Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalidomide represents a recent and innovative therapeutic approach in multiple myeloma. Main toxicity usually consists in somnolence, constipation, peripheral neuropathy and deep vein thrombosis, but, unlike alkylating agents, thalidomide is reported to rarely induce severe hematologic toxicity. The majority of patients developing neutropenia are heavily pretreated with three or more lines of chemotherapy. Here, we report, for the first time, clinical and laboratory data of a 66-year-old female patient with multiple myeloma at diagnosis who, after 4 weeks of thalidomide treatment, developed a grade 4 WHO neutropenia with septicemia. A brief review of the literature and suggestions for possible predictive factors of this toxicity are made.
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PMID:Low-dose thalidomide-induced agranulocytosis in a multiple myeloma patient treated at diagnosis. 1626 90

Early deep venous thrombosis (DVT) resolution is associated with neutrophil (PMN) influx. This study examined the role of PMNs in thrombus neovascularization and vein wall injury after DVT. A rat model of DVT by inferior vena cava (IVC) ligation was performed with control serum or rabbit anti-rat PMN serum administered perioperatively with sacrifice at 2 and 7 days. At 2 days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and 1.4-fold higher femoral venous pressures by water manometry (P = .008) but no difference in thrombus neovascularization was observed. By 7 days, DVT sizes were similar, but vein wall injury persisted in the neutropenic rats with a 2.0-fold increase in vein wall stiffness by microtensiometry (P < .05), as well as a 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors were significantly increased in neutropenic IVC at 7 days (all P < .05). Vein wall and intrathrombus uPA byWestern immunoblotting, and intrathrombus MMP-9 gelatinase activity were significantly less in neutropenic rats than controls (P < .001). Conversely, MMP-2 was significantly elevated in neutropenic IVC at 2 days after DVT. However, neutropenia induced 24 hours after DVT formation resulted in no significant increase in vein wall stiffness or collagen levels at 7 days, despite 1.4-fold larger thrombi (P < .05). These data suggest a critical early role for PMN in post DVT vein wall remodeling.
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PMID:Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization. 1649 89

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.
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PMID:Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer. 1704

We present a young woman who was diagnosed as primary antiphospholipid syndrome (deep vein thrombosis and pulmonary embolism in 1999; moderate thrombocytopenia with high-positive anticardiolipin ELISA tests in 2002, and cerebral thrombosis in 2003), and then developed hairy cell leukemia (massive splenomegaly, neutropenia, hairy cells in blood smear and bone marrow trephine biopsy in 2004). A partial remission was achieved with interferon-alpha 2a therapy. After the initiation of 2-chloro-deoxyadenosine therapy, splenomegaly disappeared, the percentage of hairy cells on the bone marrow reduced below 1%, platelet count returned to normal levels. After complete remission was achieved for hairy cell leukemia proved by bone marrow trephine biopsy, antiphospholipid antibodies were found to be negative, and no further thromboembolic complications and thrombocytopenia were seen. In our literature search, we found only six cases that had both antiphospholipid antibodies and hairy cell leukemia. Our case is the first case of antiphospholipid syndrome before the development of hairy cell leukemia. Both hairy cell leukemia and antiphospholipid syndrome responded to lymphocytotoxic treatment with 2-chloro-deoxyadenosine.
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PMID:Development of hairy cell leukemia in a patient with antiphospholipid syndrome. 1743 36

We previously reported that daily dose pomalidomide (CC-4047), a thalidomide analogue, has excellent anti-myeloma activity but is associated with myelosuppression and deep vein thrombosis. We report here a phase 1 study to determine the maximum tolerated dose (MTD) of pomalidomide at 1 mg, 2 mg, 5 mg and 10 mg on alternate days (ad). Twenty patients with relapsed myeloma were treated. Grade 4 neutropenia occurred in all patients receiving 10 mg and the MTD was defined as 5 mg ad. No thrombotic events were observed. Pomalidomide was continued following the 4-week MTD study in 17/20 patients for a median of 14 months. 10% of patients had a complete response and >50% reduction in paraprotein was achieved in 50% of subjects. Progression-free survival was 10.5 months and median overall survival was 33 months. A significant rise was observed in the proportion of CD8(+) cells. Alternate day pomalidomide was associated with a marked reduction in the incidence of thrombosis whilst maintaining excellent anti-myeloma activity. This trial provides further in vivo evidence that pomalidomide modulates the immune system in myeloma patients. Phase 2 studies to further assess the optimal schedule of administration and anti-myeloma activity of this agent are planned.
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PMID:Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. 1832 65

We previously reported a pilot study of thalidomide monotherapy for Japanese patients with refractory or relapsed multiple myeloma. In the present work, we have extended this clinical trial to a single-institute phase 2 study with a larger number of patients and longer follow-up time. New information on the optimal dose and prognostic factors as well as the correlation of toxicities with treatment schedule was obtained. Fifteen of 56 (27%) patients achieved a partial response, including three cases with near-complete remission. Most patients suffered toxicities at a dose of 400 mg per day, but there was no clear dose-response relationship. Thus, a lower dose such as 200 mg per day or less is considered optimal. Multivariate analyses identified only lack of response to therapy as an adverse prognostic factor for progression-free survival. Chromosomal abnormality, C-reactive protein >10 mg/L, and more than six previous courses of chemotherapy were significantly associated with shorter overall survival. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 23 and 11% of patients, respectively. Grade 4 interstitial pneumonia and grade 5 pulmonary hypertension were observed; however, no patient suffered deep vein thrombosis, which has frequently been observed in other studies. Duration of therapy was closely related to the development of peripheral neuropathy. The efficacy and prognostic factors of this treatment were confirmed in long-term observation. However, special attention should be paid to toxicities such as hematological and pulmonary complications as well as peripheral neuropathy in long-term users.
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PMID:Single-institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: prognostic factors and unique toxicity profile. 1838 32

Indwelling central venous catheters (CVCs) are used in the management of hematologic patients. However, insertion and maintenance of CVCs are susceptible to complications. Study design and methods data concerning 388 consecutive catheterisations, performed in oncohematologic patients between April 2003 and December 2004, were prospectively collected. At insertion thrombocytopenia was present in 109 cases (28.1%) and neutropenia in 67 (17.3%). Hemorrhage after CVC insertion occurred in five thrombocytopenic patients (1.3%). The median duration of catheterisation was 18.8 days (range 1-89), longer in the 7-French CVCs utilised in leukemic patients (24.3 days) and shorter in 12-French CVCs (11 days), used for PBSC harvesting. Deep venous thrombosis was diagnosed in 13 cases (3.3%). Ninety-two catheterisations (12.6/1000 days-catheter) were complicated by infections: 19 local infections (4.8%) and 73 (18.8%) bacteraemias of which 45 (11.6%) were catheter-related, mainly due to Gram positive germs (32/45, 71.1%). The frequency of catheter-related bacteraemia was 7.2 events/1000 days-catheter. Thirteen CVCs were removed due to thrombosis, 15 due to infections, 20 due to malfunction, the remaining 333 at patients discharge. At univariate analysis high-dose chemotherapy (p = 0.013), 7-Fr lumen (p = 0.023), acute myeloid leukemia (AML) (p = 0.001), duration of neutropenia >10 days and length of catheterisation were significantly correlated to infection. Multivariate analysis confirmed the duration of catheterisation, AML and high-dose chemotherapy as risk factors. Even though hematological in-patients are at increased risk for bleeding and infections, non-tunnelled CVCs offer a safe venous access also in patients affected by severe thrombocytopenia and prolonged neutropenia.
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PMID:Prospective monocentric study of non-tunnelled central venous catheter-related complications in hematological patients. 1902 Oct 58

To obtain approval from the Ministry of Health, Labor and Welfare of Japan, a phase II study was conducted to assess the pharmacokinetics and pharmacodynamics of thalidomide along with its efficacy and safety in Japanese patients with multiple myeloma. Between 2005 and 2006, 42 patients were enrolled, and 37 patients met eligibility criteria. Of the 37 patients, 3 were excluded from efficacy analysis because of short duration of thalidomide administration (<4 weeks). The overall response rate was 35.3% (12/34), including partial response of 14.7% (5/34) and minimal response of 20.6% (7/34). The adverse events observed in high frequency (>40%) were leukopenia, neutropenia, drowsiness, dry mouth, and constipation. Grade 3 neutropenia was observed in nine cases. Peripheral neuropathy and eruption were observed in about one-quarter of the patients. Deep vein thrombosis was not observed. At a single oral dose of thalidomide (100 mg), the C (max) was 1.68 +/- 0.41 microg/ml, T (max) was 4.54 +/- 1.71 h, T (1/2) was 4.86 +/- 0.44 h, and AUC was 15.87 +/- 3.05 microg h/ml. Low-dose thalidomide was an effective and tolerable treatment for Japanese patients with relapsed/refractory myeloma. Leukopenia and neutropenia were the most serious adverse events. The pharmacokinetics was similar to those observed in Caucasian patients.
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PMID:Phase II and pharmacokinetic study of thalidomide in Japanese patients with relapsed/refractory multiple myeloma. 1939 82

(1) Bortezomib prolongs survival in patients with relapsed or refractory multiple myeloma by a few months, but it provokes frequent and sometimes severe adverse effects. Thalidomide is generally used as a last resort; (2) Lenalidomide, a structural analogue of thalidomide, is licensed for the treatment of multiple myeloma, in combination with dexamethasone, after failure of the initial treatment regimen; (3) There are no comparative trials versus bortezomib or thalidomide; (4) Combined analysis of 2 randomised double-blind trials of lenalidomide + dexamethasone versus placebo + dexamethasone in a total of 704 patients showed that adding lenalidomide to dexamethasone slightly increased the one-year survival rate, from 75% to 82%. When this combination was used, the median time to tumour progression was 11 months. In clinical trials, the median time to tumour progression was about 2 years with thalidomide and 8 months with bortezomib; (5) In clinical trials, lenalidomide, like thalidomide, provoked deep venous thrombosis (9% versus 4% with placebo) and pulmonary embolism (4% versus 1%). Lenalidomide, unlike thalidomide, does not appear to cause peripheral neuropathy, but it does provoke cardiac arrhythmia such as atrial fibrillation (18% versus 11% with placebo) and severe haematological disorders, including neutropenia (35% versus 3% with placebo), thrombocytopenia (13% versus 6%) and anaemia (11% versus 6%); (6) The teratogenic effect of lenalidomide has not been adequately documented; (7) Lenalidomide costs about 40% more than bortezomib in France; (8) In patients with relapsed or refractory multiple myeloma there is no evidence that lenalidomide has a more favourable risk-benefit balance than bortezomib or even thalidomide.
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PMID:Lenalidomide: new drug. Myeloma: many questions remain unanswered. 1942 42

The aim of the study was to determine the efficacy and toxicity of alternate week concurrent 5-fluorouracil, hydroxyurea, and cisplatin with radiotherapy for locally advanced pancreatic adenocarcinoma. Patients received 5-fluorouracil, hydroxyurea and cisplatin with radiotherapy on an alternate week basis. Chemoradiotherapy was given day 1-5, and no therapy given day 6-14 for each 14 day cycle. Chemotherapy doses were as follows: hydroxyurea 1 mg every 12 h starting day 0, 5-fluorouracil 800 mg/m(2)/day for 5 days starting day 1, and cisplatin 20 mg/m(2) daily for 5 days every other cycle. A radiation dose of 6000 cGy was prescribed. Acute toxicities were monitored and therapy modified for hematologic toxicity. Nine patients enrolled, however eight were evaluable; one patient expired prior to therapy. The median radiation dose delivered was 5540 cGy. Sixty-three percent required a chemotherapy dose reduction. Fifty percent achieved local control by radiographic imaging after completion of therapy. Median survival was 12 months. Acute toxicity included: 38% grade 2-3 nausea, 37% grade 2-3 vomiting, 63% grade 2-3 mucositis, 63% grade 2-3 neutropenia, and 88% grade 3-4 thrombocytopenia. Other sequelae included hand-foot syndrome, deep venous thrombosis, hearing loss, seizures, and anorexia. Patients achieved the same median survival as compared to other reported studies of radiation therapy with single agent 5-fluorouracil. We do not recommend this protocol due to the significant toxicity. Future studies to incorporate conformal radiation therapy with more active, less toxic chemotherapeutic agents should be investigated.
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PMID:Concomitant 5-FU, hydroxyurea and cisplatin with external beam radiation therapy for locally advanced pancreatic cancer. 2159 Jan 58


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